DESCRIPTION: This proposal outlines experiments designed to further understand the molecular structure and function of two classes of intercellular junctions, gap junctions and tight junctions. There are five specific aims. First, the investigators will use Cx37 -/- transgenic mice to study the signalling between granulosa and oocyte, and assess the role of cAMP in meiosis. Second, they will use KO Cx37 and KO Cx40 animals to study the role of those connexins on endothelial function. Third, the maternally inherited mRNA coding for Cx38 will be ablated and the developmental consequences to embryos will be studied. Fourth, dominant negative mutants of occludin, ZO1 and ZO2 will be used to study the role of those proteins in the Xenopus embryo. Finally, as a fifth specific aim, the possible role of Cx33 in a form of CMTX associated with mental retardation will be studied, and Cx33 KO mice will be generated.